title: Sphingosylphosphorylcholine stimulates CCL2 production from human umbilical vein endothelial cells.
abstract: Sphingosylphosphorylcholine (SPC) is a component of high-density lipoprotein particles. We investigated the functional role of SPC in HUVECs. SPC stimulation induced production of the CCL2 chemokine in a PTX-sensitive G-protein-dependent manner. SPC treatment caused the activation of NF-κB and AP-1, which are essential for SPC-induced CCL2 production, and induced the activation of three MAPKs, ERK, p38 MAPK, and JNK. Inhibition of p38 MAPK or JNK by specific inhibitors caused a dramatic decrease in SPC-induced CCL2 production. The Jak/STAT3 pathway was also activated upon SPC stimulation of HUVECs. Pretreatment with a Jak inhibitor blocked not only SPC-induced p38 MAPK and JNK activation, but also NF-κB and AP-1 activation. Our results suggest that SPC stimulates HUVECs, resulting in Jak/STAT3-, NF-κB-, and AP-1-mediated CCL2 production. We also observed that SPC stimulated expression of the adhesion molecule ICAM-1 in HUVECs. Our results suggest that SPC may contribute to atherosclerosis; therefore, SPC and its unidentified target receptor offer a starting point for the development of a treatment for atherosclerosis.
authors.affiliation: Cancer Research Institute, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Sang Doo
authors.initials: SD
authors.lastname: Kim
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Shim
authors.forename: Hak Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Su
authors.initials: YS
authors.lastname: Jung
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kwon
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D037342:Pertussis Toxin / Q000502:physiology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008563:Membrane Lipids; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D037342:Pertussis Toxin; D013110:Sphingosine